[Community-acquired pneumonia]. / Ambulant erworbene Pneumonie.

RISK FACTORS FOR SEVERE COURSES: The CRB-65 score is recommended as a risk predictor, as well as consideration of unstable comorbidities and oxygenation. GROUPING OF COMMUNITY-ACQUIRED PNEUMONIA: Community-acquired pneumonia is divided into 3 groups: mild pneumonia, moderate pneumonia, severe pneumonia. Whether there is a curative vs palliative treatment goal should be determined early. DIAGNOSTIC RECOMMENDATION: An X-ray chest radiograph is recommended to confirm the diagnosis, also in the outpatient setting if possible. Sonography of the thorax is an alternative, asking for additional imaging if negative. Streptococcus pneumoniae remains the most common bacterial pathogen. THERAPY: Community-acquired pneumonia continues to be associated with high morbidity and lethality. Prompt diagnosis and prompt initiation of risk-adapted antimicrobial therapy are essential measures. However, in times of COVID-19, as well as the current influenza and RSV epidemic, purely viral pneumonias must also be expected. At least with COVID-19, antibiotics can often be avoided. Antiviral and anti-inflammatory drugs are used here. POST-ACUTE COURSE: Patients after community-acquired pneumonia have increased acute and long-term mortality due to cardiovascular events in particular. The focus of research is on improved pathogen identification, a better understanding of the host response with the potential of developing specific therapeutics, the role of comorbidities, and the long-term consequences of the acute illness.

[Advances in epidemiology, etiology, and treatment of community-acquired pneumonia].

Community-acquired pneumonia (CAP) is the third leading cause of death worldwide and one of the most commonly infectious diseases. Its epidemiological characteristics vary with host and immune status, and corresponding pathogen spectrums migrate over time and space distribution. Meanwhile, with the outbreak of COVID-19, some unconventional treatment strategies are on the rise. This article reviewed the epidemiological characteristics, pathogen spectrum and treatment direction of CAP in China over the years, and aimed to provide guidance for the diagnosis and treatment of CAP in clinical practice.

Unmet needs in pneumonia research: a comprehensive approach by the CAPNETZ study group.

INTRODUCTION: Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The "network of excellence on Community Acquired Pneumonia" (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research. METHODS: To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat. RESULTS: Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications. CONCLUSION: Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients' risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.

Ventilator-associated pneumonia is linked to a worse prognosis than community-acquired pneumonia in children.

BACKGROUND: Around 12-20% of patients with community-acquired pneumonia (CAP) require critical care. Ventilator-associated pneumonia (VAP) is the second cause of nosocomial infection in Paediatric Intensive Care Units (PICU). As far as we know, there are no studies comparing both types of pneumonia in children, thus it remains unclear if there are differences between them in terms of severity and outcomes. OBJECTIVE: The aim was to compare clinical and microbiological characteristics and outcomes of patients with severe CAP and VAP. METHODS: A retrospective descriptive study, including patients diagnosed of VAP and CAP, with a positive respiratory culture and under mechanical ventilation, admitted to the PICU from 2015 to 2019. RESULTS: 238 patients were included; 163 (68.4%) with CAP, and 75 (31.5%) with VAP. Patients with VAP needed longer mechanical ventilation (14 vs. 7 days, p<0.001) and more inotropic support (49.3 vs. 30.7%, p = 0.006). Patients with VAP had higher mortality (12 vs. 2.5%, p = 0.005). Enterobacterales were more involved with VAP than with CAP (48 vs. 9%, p<0.001). Taking into account only the non-drug sensitive microorganisms, patients with VAP tended to have more multidrug-resistant bacteria (30 vs. 10.8%, p = 0.141) than patients with CAP. CONCLUSION: Patients with VAP had worse prognosis than patients with CAP, needing longer mechanical ventilation, more inotropic support and had higher mortality. Patients with VAP were mainly infected by Enterobacterales and had more multidrug resistant microorganisms than patients with CAP.

Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non- SARS-CoV-2 community-acquired pneumonia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD. METHODS: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality. RESULTS: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death. CONCLUSION: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality.

The clinical role of host and bacterial-derived extracellular vesicles in pneumonia.

Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.

The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design.

There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).

Neonates Hospitalized with Community-Acquired SARS-CoV-2 in a Colorado Neonatal Intensive Care Unit.

IMPORTANCE: The novel coronavirus 2019 (SARS-CoV-2) has been well described in adults. Further, the impact on older children and during the perinatal time is becoming better studied. As community spread increases, it is important to recognize that neonates are vulnerable to community spread as well. The impact that community-acquired SARS-CoV-2 has in the neonatal time period is unclear, as this population has unique immunity considerations. OBJECTIVE: To report on a case series of SARS-CoV-2 in neonates through community acquisition in the USA. DESIGN: This is an early retrospective study of patients admitted to the Neonatal Intensive Care Unit (NICU) identified as having SAR-CoV-2 through positive real-time polymerase chain reaction assay of nasopharyngeal swabs. FINDINGS: Three patients who required admission to the NICU between the ages of 17 and 33 days old were identified. All 3 had ill contacts in the home or had been to the pediatrician and presented with mild to moderate symptoms including fever, rhinorrhea, and hypoxia, requiring supplemental oxygen during their hospital stay. One patient was admitted with neutropenia, and the other 2 patients became neutropenic during hospitalization. None of the patients had meningitis or multiorgan failure. CONCLUSIONS AND RELEVANCE: Infants with community-acquired SARS-CoV-2 may require hospitalization due to rule-out sepsis guidelines if found to have fever and/or hypoxia. Caregivers of neonates should exercise recommended guidelines before contact with neonates to limit community spread of SARS-CoV-2 to this potentially vulnerable population, including isolation, particularly as asymptomatic cases become prevalent.

Implementation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial in a US health system-lessons learned and recommendations.

BACKGROUND: The Randomized Embedded Multifactorial Adaptive Platform for COVID-19 (REMAP-COVID) trial is a global adaptive platform trial of hospitalized patients with COVID-19. We describe implementation at the first US site, the UPMC health system, and offer recommendations for implementation at other sites. METHODS: To implement REMAP-COVID, we focused on six major areas: engaging leadership, trial embedment, remote consent and enrollment, regulatory compliance, modification of traditional trial management procedures, and alignment with other COVID-19 studies. RESULTS: We recommend aligning institutional and trial goals and sharing a vision of REMAP-COVID implementation as groundwork for learning health system development. Embedment of trial procedures into routine care processes, existing institutional structures, and the electronic health record promotes efficiency and integration of clinical care and clinical research. Remote consent and enrollment can be facilitated by engaging bedside providers and leveraging institutional videoconferencing tools. Coordination with the central institutional review board will expedite the approval process. Protocol adherence, adverse event monitoring, and data collection and export can be facilitated by building electronic health record processes, though implementation can start using traditional clinical trial tools. Lastly, establishment of a centralized institutional process optimizes coordination of COVID-19 studies. CONCLUSIONS: Implementation of the REMAP-COVID trial within a large US healthcare system is feasible and facilitated by multidisciplinary collaboration. This investment establishes important groundwork for future learning health system endeavors. TRIAL REGISTRATION: NCT02735707 . Registered on 13 April 2016.

Applying the lessons learned from coronavirus disease 2019 to improve pneumonia management.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has produced an extraordinary amount of literature in a short time period. This review focuses on what the new literature has provided in terms of more general information about the management of community-acquired pneumonia (CAP). RECENT FINDINGS: Measures taken to reduce the spread of COVID-19 have caused a significant drop in influenza worldwide. Improvements in imaging, especially ultrasound, and especially in the application of rapid molecular diagnosis are likely to have significant impact on the management of CAP. Therapeutic advances are so far limited. SUMMARY: COVID-19 has taught us that we can do far more to prevent seasonal influenza and its associated mortality, morbidity and economic cost. Improvements in imaging and pathogen diagnosis are welcome, as is the potential for secondary benefits of anti-COVID-19 therapies that may have reach effect on respiratory viruses other than severe acute respiratory syndrome coronavirus 2. As community-transmission is likely to persist for many years, recognition and treatment of severe acute respiratory syndrome coronavirus 2 will need to be incorporated into CAP guidelines moving forward.

[Diagnosis and treatment of community-acquired pneumonia in elderly patients combined with coronavirus disease 2019: analysis of 1 case].

OBJECTIVE: To explore the pathological characteristics and outcomes of elderly patients with community acquired pneumonia (CAP) accompanied by coronavirus disease 2019 (COVID-19). METHODS: The diagnosis and treatment process of one elderly patient with CAP accompanied by COVID-19 who was admitted to COVID-19 Treatment Center of Liaoning Province on February 7, 2020 were reviewed. The experience of treatment by analyzing the characteristics of such type of patients during diagnosis and treatment were summarized. RESULTS: A female patient, aged 79 years ald, was admitted to the Center with following features: fever, dry cough, fatigue with dyspnea, scattered moist rales in both lungs, oxygenation index (PaCO2/FiO2) of 95 mmHg (1 mmHg = 0.133 kPa), and diffuse interstitial pneumonia in both lungs indicated by chest CT, of which the majority were ground glass-like and fibrous lesions. It was confirmed to be consistent with the feature of severe COVID-19 cases. The patient was successfully cured one month later following anti-inflammatory, anti-viral and high-flow oxygen therapies, homeostasis maintenance of the body, psychological counseling, etc. Accordingly, the treatment experience in CAP combined with COVID-19 in the elderly patients was summarized as follows. In respiratory system, the timing of high-flow oxygen therapy and mechanical ventilation should be seized. As for anti-inflammatory and antiviral therapy, attention should be paid to the treatment of CAP as well as antiviral therapy and symptomatic and supportive therapy. With the progression of the disease, the production of drug-resistant bacteria and the possibility of fungal infection should be paid attention to. For the circulatory system, we should pay attention to the stability of fluid volume and internal environment, and strengthen hemodynamic monitoring and bedside ultrasound to evaluate the cardiovascular capacity-load. In the aspect of the immune system, the selection of the application time of immune-enhancers and glucocorticoids should be paid attention to. In terms of enteral nutrition, early low-fat and high-protein diet is conducive to the recovery of intestinal function and the prevention of bacterial translocation. In addition to the protection of the function of important organs, therapies such as reasonable sedation and psychological intervention should also be used. CONCLUSIONS: Elderly patients with CAP accompanied by COVID-19 have complicated conditions and high degree of difficulty in treatment. Comprehensive evaluation of the disease as well as synthetic and effective intervention are the key factors of successful treatment of such patients.

Recognition and management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19.

In COVID-19, respiratory infection with SARS-CoV-2 plus another virus (viral co-infection) or with SARS-CoV-2 plus a bacterial pathogen (combined viral and bacterial pneumonia) has been described. Secondary bacterial pneumonia can follow the initial phase of viral respiratory infection or occur during the recovery phase. No obvious pattern or guidelines exist for viral co-infection, combined viral and bacterial pneumonia, or secondary bacterial pneumonia in COVID-19. Based on existing clinical data and experience with similar viruses such as influenza and SARS-CoV, the management approach in COVID-19 should, ideally, take into consideration the overall presentation and the trajectory of illness.

Comparison of clinical characteristics between coronavirus disease 2019 pneumonia and community-acquired pneumonia.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has high morbidity and mortality, and spreads rapidly in the community to result in a large number of infection cases. This study aimed to compare clinical features in adult patients with coronavirus disease 2019 (COVID-19) pneumonia to those in adult patients with community-acquired pneumonia (CAP). METHODS: Clinical presentations, laboratory findings, imaging features, complications, treatment and outcomes were compared between patients with COVID-19 pneumonia and patients with CAP. The study group of patients with COVID-19 pneumonia consisted of 120 patients. One hundred and thirty-four patients with CAP were enrolled for comparison. RESULTS: Patients with COVID-19 pneumonia had lower levels of abnormal laboratory parameters (white blood cell count, lymphocyte count, procalcitonin level, erythrocyte sedimentation rate and C-reactive protein level) and more extensive radiographic involvement. More severe respiratory compromise resulted in a higher rate of intensive care unit admission, acute respiratory distress syndrome (ARDS) and mechanical ventilation (36% vs 15%, 34% vs 15% and 32% vs 12%, respectively; all p < .05). The 30 day mortality was more than twice as high in patients with COVID-19 pneumonia (12% versus 5%; p = .063), despite not reaching a statistically significant difference. CONCLUSIONS: Lower levels of abnormal laboratory parameters, more extensive radiographic involvement, more severe respiratory compromise, and higher rates of ICU admission, ARDS and mechanical ventilation are key characteristics that distinguish patients with COVID-19-associated pneumonia from patients with CAP.

Acute oxygen therapy: a cross-sectional study of prescribing practices at an English hospital immediately before COVID-19 pandemic.

BACKGROUND: Approximately 14% of UK hospital in-patients receive supplemental oxygen therapy, only 57% have valid prescriptions. Oxygen must be optimally prescribed to ensure maximal therapeutic response whilst minimizing adverse outcomes (including fatality). This study investigates prescription compliance. METHODS: All adults admitted to medical wards (18 February to 3 March 2020) were included. Analyses present proportions, descriptive statistics, and hypothesis testing. Ethical approval was unnecessary for this audit. RESULTS: Of the 636 patients admitted, 66 (10%) were receiving oxygen therapy. Ages ranged from 34 to 100 years with 36 (54.5%) males and 30 (45.5%) females. The prescription was not documented in the oxygen section of the drug chart (n = 37, 56.1%, p = 0.389), nor did it have the physicians signature (n = 40, 60.6%, p = 0.110) nor date (n = 46, 69.7%, p = 0.002). Thirteen chronic obstructive pulmonary disease (COPD) patients (19.7%) were at risk of hypercapnic failure (p = 1.582x10-6). Target oxygen saturation (SpO2) range had been documented for 30 (45.5%) patients. A target SpO2 range of 88-92% was documented for 9 patients (13.6%), a 94-98% range documented for 11 patients (16.7%). All patients had an invalid prescription. CONCLUSION: We present real-world practice in naturalistic settings, immediately before pandemic-lockdown. Enhanced compliance is advocated to reduce risks of harm and mortality.

Critical care management of adults with community-acquired severe respiratory viral infection.

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.